Since 1998, we have been collaborating on research on fetal alcohol syndrome (FAS) in Cape Town, South Africa, where the incidence of FAS is among the highest in the world. In 2005 we were funded to implement the first fMRI studies in South Africa and in 2008 were awarded an R01 to use neuroimaging in school-age children to examine the cerebellar neural circuitry related to eyeblink conditioning (EBC), which we recently identified as a strikingly reliable potential biomarker of FAS and other alcohol-related disorders. The R01 also includes funding to recruit heavy drinking pregnant women and controls for a neurobehavioral study of EBC at 6 months postpartum. Fetal alcohol spectrum disorder, a world-wide public health problem whose long-term effects include significant neurocognitive impairment, is difficult to diagnose in infancy. Magnetic resonance imaging (MRI) studies with adults and children have shown that specific brain regions are disproportionately affected. Volumetric MRI measures in the first weeks of life may detect early differences in regional volumes and provide a more sensitive index of future neurological outcome than standard newborn behavioral or neurological examinations. To date, few studies have been conducted using MRI cerebral morphometry segmentation in neonates, which currently requires hand labeling and is, therefore, too labor intensive for large data sets. We propose to conduct the first structural MRI study in newborns exposed prenatally to alcohol. Two groups of pregnant women will be recruited-35 heavy alcohol users and 35 non-exposed controls. The aims are (1) to determine which brain structures are disproportionately smaller in neonates with heavy prenatal alcohol exposure; (2) to test whether prenatal exposure- related volumetric reductions in specific neonatal brain regions predict neurobehavioral performance deficits at 6 months; and (3) to use information-theoretic registration techniques to examine alterations in shape and location of specific brain structures in prenatally exposed neonates. An atlas will be constructed from the data from healthy neonatal controls to validate and refine automated segmentation tools currently being developed at Massachusetts General Hospital to permit faster and more efficient labeling of infant brain structures.